scholarly journals The Impact of miRNAs in Health and Disease of Retinal Pigment Epithelium

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniela Intartaglia ◽  
Giuliana Giamundo ◽  
Ivan Conte
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Therapeutic Approaches ◽  
Pathological Conditions ◽  
Health And Disease ◽  
Non Coding Rnas ◽  
The Impact

MicroRNAs (miRNAs), a class of non-coding RNAs, are essential key players in the control of biological processes in both physiological and pathological conditions. miRNAs play important roles in fine tuning the expression of many genes, which often have roles in common molecular networks. miRNA dysregulation thus renders cells vulnerable to aberrant fluctuations in genes, resulting in degenerative diseases. The retinal pigment epithelium (RPE) is a monolayer of polarized pigmented epithelial cells that resides between the light-sensitive photoreceptors (PR) and the choriocapillaris. The demanding physiological functions of RPE cells require precise gene regulation for the maintenance of retinal homeostasis under stress conditions and the preservation of vision. Thus far, our understanding of how miRNAs function in the homeostasis and maintenance of the RPE has been poorly addressed, and advancing our knowledge is central to harnessing their potential as therapeutic agents to counteract visual impairment. This review focuses on the emerging roles of miRNAs in the function and health of the RPE and on the future exploration of miRNA-based therapeutic approaches to counteract blinding diseases.

scholarly journals Regulation of phagolysosomal activity by miR-204 critically influences structure and function of retinal pigment epithelium/retina

2019 ◽  
Vol 28 (20) ◽  
pp. 3355-3368 ◽  
Author(s):  
Congxiao Zhang ◽  
Kiyoharu J Miyagishima ◽  
Lijin Dong ◽  
Aaron Rising ◽  
Malika Nimmagadda ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Primary Cultures ◽  
Structure And Function ◽  
Apical Surface ◽  
Altered Expression ◽  
And Function ◽  
The Impact

Abstract MicroRNA-204 (miR-204) is expressed in pulmonary, renal, mammary and eye tissue, and its reduction can result in multiple diseases including cancer. We first generated miR-204−/− mice to study the impact of miR-204 loss on retinal and retinal pigment epithelium (RPE) structure and function. The RPE is fundamentally important for maintaining the health and integrity of the retinal photoreceptors. miR-204−/− eyes evidenced areas of hyper-autofluorescence and defective photoreceptor digestion, along with increased microglia migration to the RPE. Migratory Iba1+ microglial cells were localized to the RPE apical surface where they participated in the phagocytosis of photoreceptor outer segments (POSs) and contributed to a persistent build-up of rhodopsin. These structural, molecular and cellular outcomes were accompanied by decreased light-evoked electrical responses from the retina and RPE. In parallel experiments, we suppressed miR-204 expression in primary cultures of human RPE using anti-miR-204. In vitro suppression of miR-204 in human RPE similarly showed abnormal POS clearance and altered expression of autophagy-related proteins and Rab22a, a regulator of endosome maturation. Together, these in vitro and in vivo experiments suggest that the normally high levels of miR-204 in RPE can mitigate disease onset by preventing generation of oxidative stress and inflammation originating from intracellular accumulation of undigested photoreactive POS lipids. More generally, these results implicate RPE miR-204-mediated regulation of autophagy and endolysosomal interaction as a critical determinant of normal RPE/retina structure and function.

scholarly journals A Multi-Omics Approach Identifies Key Regulatory Pathways Induced by Long-Term Zinc Supplementation in Human Primary Retinal Pigment Epithelium

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3051
Author(s):  
Eszter Emri ◽  
Elod Kortvely ◽  
Sascha Dammeier ◽  
Franziska Klose ◽  
David Simpson ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Zinc Supplementation ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Gene Set Enrichment Analysis ◽  
Age Related Macular Degeneration ◽  
Molecular Networks ◽  
Molecular Pathways ◽  
Regulatory Pathways

In age-related macular degeneration (AMD), both systemic and local zinc levels decline. Elevation of zinc in clinical studies delayed the progression to end-stage AMD. However, the molecular pathways underpinning this beneficial effect are not yet identified. In this study, we used differentiated primary human fetal retinal pigment epithelium (RPE) cultures and long-term zinc supplementation to carry out a combined transcriptome, proteome and secretome analysis from three genetically different human donors. After combining significant differences, we identified the complex molecular networks using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). The cell cultures from the three donors showed extensive pigmentation, development of microvilli and basal infoldings and responded to zinc supplementation with an increase in transepithelial electrical resistance (TEER) (apical supplementation: 443.2 ± 79.3%, basal supplementation: 424.9 ± 116.8%, compared to control: 317.5 ± 98.2%). Significant changes were observed in the expression of 1044 genes, 151 cellular proteins and 124 secreted proteins. Gene set enrichment analysis revealed changes in specific molecular pathways related to cell adhesion/polarity, extracellular matrix organization, protein processing/transport, and oxidative stress response by zinc and identified a key upstream regulator effect similar to that of TGFB1.

scholarly journals The Impact of cHS4 Insulators on DNA Transposon Vector Mobilization and Silencing in Retinal Pigment Epithelium Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e48421 ◽  
Author(s):  
Nynne Sharma ◽  
Anne Kruse Hollensen ◽  
Rasmus O. Bak ◽  
Nicklas Heine Staunstrup ◽  
Lisbeth Dahl Schrøder ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Dna Transposon ◽  
Retinal Pigment Epithelium Cells ◽  
The Impact ◽  
Epithelium Cells

scholarly journals Polyphenol Metabolite Pyrogallol-O-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina

2021 ◽  
Vol 22 (21) ◽  
pp. 11402
Author(s):  
Daniela F. Santos ◽  
Mariana Pais ◽  
Cláudia N. Santos ◽  
Gabriela A. Silva
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Diabetic Mouse ◽  
Mouse Retina ◽  
Rpe Cells ◽  
Glut 1 ◽  
Diabetic Retina ◽  
The Impact ◽  
Epithelium Cells

(Poly)phenol-derived metabolites are small molecules resulting from (poly)phenol metabolization after ingestion that can be found in circulation. In the last decade, studies on the impact of (poly)phenol properties in health and cellular metabolism accumulated evidence that (poly)phenols are beneficial against human diseases. Diabetic retinopathy (DR) is characterized by inflammation and neovascularization and targeting these is of therapeutic interest. We aimed to study the effect of pyrogallol-O-sulfate (Pyr-s) metabolite in the expression of proteins involved in retinal glial activation, neovascularization, and glucose transport. The expression of PEDF, VEGF, and GLUT-1 were analyzed upon pyrogallol-O-sulfate treatment in RPE cells under high glucose and hypoxia. To test its effect on a diabetic mouse model, Ins2Akita mice were subjected to a single intraocular injection of the metabolite and the expression of PEDF, VEGF, GLUT-1, Iba1, or GFAP measured in the neural retina and/or retinal pigment epithelium (RPE), two weeks after treatment. We observed a significant decrease in the expression of pro-angiogenic VEGF in RPE cells. Moreover, pyrogallol-O-sulfate significantly decreased the expression of microglial marker Iba1 in the diabetic retina at different stages of disease progression. These results highlight the potential pyrogallol-O-sulfate metabolite as a preventive approach towards DR progression, targeting molecules involved in both inflammation and neovascularization.

scholarly journals Volatile Evolution of Long Non-Coding RNA Repertoire in Retinal Pigment Epithelium: Insights from Comparison of Bovine and Human RNA Expression Profiles

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 205 ◽  
Author(s):  
Olga A. Postnikova ◽  
Igor B. Rogozin ◽  
William Samuel ◽  
German Nudelman ◽  
Vladimir N. Babenko ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Expression Profiles ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Non Coding Rna ◽  
Small Set ◽  
Flexible Adaptation ◽  
Non Coding Rnas ◽  
Whole Genome Alignment ◽  
Long Non Coding Rna

Currently, several long non-coding RNAs (lncRNAs) (TUG1, MALAT1, MEG3 and others) have been discovered to regulate normal visual function and may potentially contribute to dysfunction of the retina. We decided to extend these analyses of lncRNA genes to the retinal pigment epithelium (RPE) to determine whether there is conservation of RPE-expressed lncRNA between human and bovine genomes. We reconstructed bovine RPE lncRNAs based on genome-guided assembly. Next, we predicted homologous human transcripts based on whole genome alignment. We found a small set of conserved lncRNAs that could be involved in signature RPE functions that are conserved across mammals. However, the fraction of conserved lncRNAs in the overall pool of lncRNA found in RPE appeared to be very small (less than 5%), perhaps reflecting a fast and flexible adaptation of the mammalian eye to various environmental conditions.

scholarly journals Impact of drusen and drusenoid retinal pigment epithelium elevation size and structure on the integrity of the retinal pigment epithelium layer

2018 ◽  
Vol 103 (2) ◽  
pp. 227-232 ◽  
Author(s):  
Ferdinand Schlanitz ◽  
Bernhard Baumann ◽  
Stefan Sacu ◽  
Lukas Baumann ◽  
Michael Pircher ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cross Sectional Study ◽  
Age Related Macular Degeneration ◽  
Cross Sectional ◽  
Photoreceptor Layer ◽  
Age Related ◽  
The Impact ◽  
Size And Structure

PurposeTo evaluate the impact of drusen size and structure on retinal pigment epithelium (RPE) and photoreceptor layers in eyes with early to intermediate age-related macular degeneration (AMD) using polarisation-sensitive optical coherence tomography (OCT).DesignRetrospective investigation of an observational cross-sectional study.ParticipantsPatients with early to intermediate AMD.MethodsTwenty-five eyes of 25 patients with drusen were imaged with polarisation-sensitive OCT using macular volume scans. Each scan was manually graded for six distinct drusen characteristics and the integrity of both the overlying RPE and photoreceptor layer. The central scan of each single druse, as well as its diameter and location, were selected for statistical calculations.ResultsA total number of 5933 individual drusen including their adjacent RPE and photoreceptor layer were evaluated. 41.3% of all drusen demonstrated an intact overlying RPE; in 28.1% the RPE layer was irregular, but continuous. In 30.6%, the RPE layer signal was discontinuous above the area of drusen. The level of RPE alteration was significantly related to shape (p<0.001), internal reflectivity (p<0.001) and homogeneity (p<0.001) of the drusen and their diameter, with a higher probability for larger drusen to have a discontinuous RPE (OR 3.2, p<0.001). The number of drusen showing overlying foci or an altered photoreceptor layer was too small to be conclusive, but showed a trend towards an altered RPE if present.ConclusionsPolarisation-sensitive OCT reveals a correlation between specific drusen characteristics and the integrity of the overlying RPE layer. Drusen diameter and configuration were significantly associated with RPE loss.

scholarly journals Fine Tuning of an Oxidative Stress Model with Sodium Iodate Revealed Protective Effect of NF-κB Inhibition and Sex-Specific Difference in Susceptibility of the Retinal Pigment Epithelium

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 103
Author(s):  
Xue Yang ◽  
Usha Rai ◽  
Jin-Yong Chung ◽  
Noriko Esumi
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelium ◽  
Low Dose ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Fine Tuning ◽  
Dose Effect ◽  
High Dose ◽  
Sodium Iodate ◽  
Quantification Method

Oxidative stress of the retinal pigment epithelium (RPE) is a major risk factor for age-related macular degeneration (AMD). As a dry AMD model via oxidative stress, sodium iodate (NaIO3), which is primarily toxic to the RPE, has often been used at a high dose to cause RPE death for studying photoreceptor degeneration. Thus, characterization of RPE damage by a low dose of NaIO3 is still limited. To quantify RPE damage caused by NaIO3 in mice, we recently developed a morphometric method using RPE flat-mounts. Here, we report that NaIO3 has a narrow range of dose–effect correlation at 11–18 mg/kg body weight in male C57BL/6J mice. We evaluated the usefulness of our quantification method in two experimental settings. First, we tested the effect of NF-κB inhibition on NaIO3-induced RPE damage in male C57BL/6J mice. IKKβ inhibitor BAY 651942 suppressed upregulation of NF-κB targets and protected the RPE from oxidative stress. Second, we tested sex-specific differences in NaIO3-induced RPE damage in C57BL/6J mice using a low dose near the threshold. NaIO3 caused more severe RPE damage in female mice than in male mice. These results demonstrate the usefulness of the quantification method and the importance of fine-tuning of the NaIO3 dose. The results also show the therapeutic potential of IKKβ inhibition for oxidative stress-related RPE diseases, and reveal previously-unrecognized sex-specific differences in RPE susceptibility to oxidative stress.

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